Adjuvant Chemoradiotherapy Improves OS vs Radiotherapy in High-Risk Endometrial Cancer

Updated findings from the PORTEC-3 clinical trial show that combining adjuvant chemotherapy with radiotherapy significantly improved overall survival (OS) and failure-free survival (FFS) rates versus radiotherapy alone in women with high-risk endometrial cancer (Lancet Oncol. 2019 Jul 22. Epub ahead of print).

“This updated analysis shows significantly improved overall survival and failure-free survival with chemoradiotherapy versus radiotherapy alone,” explained Stephanie M. de Boer, MD, Department of Radiation Oncology, Leiden University Medical Center, Netherlands, and colleagues.

They conducted the phase 3, multi-center PORTEC-3 trial to evaluate the benefit of combining adjuvant chemotherapy with radiotherapy versus pelvic radiotherapy alone in women with high-risk endometrial cancer.

“We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis,” Dr de Boer et al said.

Between November 23, 2006, and December 20, 2013, a total of 660 women with high-risk endometrial cancer were enrolled in the study if they had International Federation of Gynecology and Obstetrics 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion and/or lymphovascular space invasion; stage II or III disease; or stage I to III disease with serous or clear-cell histology.

These women were randomized in a 1:1 ratio to receive radiotherapy alone (48.6 Gy in 1.8 Gy fractions administered 5 days per week; n = 330) or chemoradiotherapy (2 cycles of cisplatin 50 mg/m² administered during radiotherapy followed by 4 cycles of carboplatin AUC5 and paclitaxel 175 mg/m²; n = 330).

The co-primary end points of the study were OS and FFS, and the secondary end points were vaginal, pelvic, and distant recurrence. Dr de Boer and colleagues analyzed survival end points by intention-to-treat and adjusted for stratification factors.

At a median follow-up of 72.6 months, the 5-year rate of OS was 81.4% (95% CI, 77.2-85.8) with chemoradiotherapy versus 76.1% (95% CI, 71.6-80.9) with radiotherapy alone (adjusted hazard ratio [HR], 0.70; 95% CI, 0.51-0.97; P = .034), and 5-year rate of FFS was 76.5% (95% CI, 71.5-80.7) versus 69.1% (95% CI, 63.8-73.8; HR, 0.70; 0.52-0.94; P = .016), respectively.

Notably, distant metastases were the primary recurrence site in most patients whose disease relapsed, occurring in 78 women in the chemoradiotherapy arm versus 98 in the radiotherapy-alone arm. In both groups, 1 patient had isolated vaginal recurrence as the first site, and isolated pelvic recurrence was the first site of recurrence in 3 women and 4 women in the chemoradiotherapy versus radiotherapy-alone arms, respectively.

At 5 years, there was only 1 grade 4 adverse event (ileus or obstruction) reported in the chemoradiotherapy arm, and grade 3 adverse events did not differ significantly between the 2 arms. Hypertension was the most common grade 3 adverse event, occurring in 2% of women in both arms.

At 5 years, adverse events of grade ≥2 were reported in 76 (38%) of 201 women in the chemoradiotherapy arm and in 43 (23%) of 187 in the radiotherapy-alone arm (P = .002).

According to the investigators, sensory neuropathy endured more often following receipt of chemoradiotherapy versus radiotherapy alone, with 5-year rates of grade ≥2 neuropathy of 6% and 0%, respectively. There were no treatment-related deaths reported.

“This treatment schedule should be discussed and recommended, especially for women with stage III or serous cancers, or both, as part of shared decision making between doctors and patients,” Dr de Boer and colleagues concluded.

“Follow-up is ongoing to evaluate long-term survival,” they said.—Hina Porcelli